CTL cells and NK cells are known as the major effector cells in the anti-tumor immune response. CTL cells can recognize and kill tumor cells expressing MHC Class I molecules and specific tumor antigens. However, the expressions of MHC Class I molecules are down regulated in many tumor tissues, and in this situation, CTL cells cannot recognize them, while NK cells expressing natural killer cell receptors will act as the main effector cells to kill tumor. NK cells and CTL cells elicit their anti-tumor effects via the binding of the receptors expressed on the surface of their cell membrane to the corresponding ligands on the surface of tumor cells which triggers the release of cytotoxic components from effector cells. Therefore, the discovery of a kind of immune cells expressing both natural killer cell receptors and T cell surface marker TCRβ/CD3, which is also known as NKT cell, has attracted great attentions in the field of immunology.
In 1987, three independent research teams reported a population of T cells expressing a moderate intensity of TCRαβ and having no expressions of CD4 and CD8[2-4], respectively; in 1990, Sykes reported a cell subpopulation which expresses both NK1.1 and TCRαβ[5]. In 1995, “NKT” cell was firstly used as a proper noun, and it especially refers to a subpopulation of T cells expressing NK1.1 (mouse, CD161c) marker[6]. According to the CD1d restriction and the TCR diversity of NKT cells, Godfrey classified mouse NKT cells into three types of populations: Type I NKT cell, Type II NKT cell and NKT-like cell. Type I NKT cell was classified as a population of NKT cells that can recognize CD1d presented α-Galcer lipid antigens, Type II NKT cell can recognize CD1d presented lipid antigens other than α-Galcer, and NKT-like cell includes other NKT cell subpopulations other than Type I NKT cell and Type II NKT cell. Among them, most extensive researches have been made on the immunological features and functions of the Type I NKT cell which is also known as a classical NKT cell; at present, most of NKT cells mentioned in the literatures are actually the classical NKT cells. With the development of CD1d tetramer technology as well as the establishment of CD1d-deficient transgenic mice, the current researches on NKT cells mostly focused on the classical NKT cell (i.e., Type I NKT cell). However, Type I NKT cell is only one population of NKT cell, and more than 50% of NKT cells are NKT-like cells[7].
Type II NKT cells is characterized that its development depends on the CD1d molecule, and yet these cells express relatively diverse TCR chains. The development of NKT-like cell does not depend on CD1d molecules, and yet NKT-like cell expresses a variety of TCR chains. However, there are few researches on the Type II NKT cells and the NKT-like cells at present. Existing researches showed that the Type II NKT cells have some immunomodulating functions, and NKT-like cells have an antitumor effect. A population of NKT-like cells which is not dependent on CD1d molecules has been found in β2 microglobulin deficient mice, and these cells can be able to kill many kinds of tumor cells in vitro[8].
However, the mechanism of the anti-tumor activity of NKT-like cells was still not elucidated based on the results from normal mice up to now. Therefore, there is a need to characterize the subpopulations of NKT-like cell that have an anti-tumor effect and its anti-tumor mechanism, so as to further study the cell subpopulations and the possibility of their clinical application.